tbuckley/cabot-search huggingface dataset:
Effect of a smartphone intervention as a secondary prevention for use among university students with unhealthy alcohol use: randomised controlled trial
Authors: Nicolas Bertholet, Elodie Schmutz, Joseph Studer, Angéline Adam, Gerhard Gmel, John A Cunningham, Jennifer McNeely, Jean-Bernard Daeppen
Journal: BMJ (2023)

Objective To estimate the effects of providing access to an alcohol intervention based on a smartphone. Design Randomised controlled trial.. Setting Four higher education institutions in Switzerland. Participants 1770 students (≥18 years) who screened positive for unhealthy alcohol use (ie, a score on the alcohol use disorders identification test-consumption (AUDIT-C) of ≥4 for men and ≥3 for women) were randomly assigned by 1:1 allocation ratio in blocks of 10. Intervention Providing access to a brief, smartphone based alcohol intervention. Outcome measures The primary outcome studied was number of standard drinks per week at six months and the secondary outcome was number of heavy drinking days (past 30 days). Additional outcomes were maximum number of drinks consumed on one occasion, alcohol related consequences, and academic performance. Follow-up assessments occurred at months three, six, and 12. Data were analysed by intention to treat and by using generalised linear mixed models with random intercepts for the recruitment site and participants nested within the recruitment site, and with intervention ( v control), time (three months v six months; 12 months v six months), and baseline outcome values as fixed effects. Results Between 26 April 26 2021 and 30 May 2022, 1770 participants (intervention group (n=884); control group (n=886)) were included. Mean age was 22.4 years (standard deviation 3.07); 958 (54.1%) were women; and 1169 (66.0%) were undergraduate students, 533 (30.1%) were studying for a master’s degree, 43 (2.4%) were studying for a doctorate, and 25 (1.4%) were students of other higher education programme. The baseline mean number of standard drinks per week was 8.59 (standard deviation 8.18); the baseline number of heavy drinking days was 3.53 (4.02). Of 1770 participants, follow-up rates were 1706 (96.4%) at three months, 1697 (95.9%) at six months, and 1660 (93.8%) at 12 months. Of 884 students randomly assigned to the intervention group, 738 (83.5%) downloaded the smartphone application. The intervention had a significant overall effect on the number of standard drinks per week (incidence rate ratio 0.90 (95% confidence interval 0.85 to 0.96)), heavy drinking days (0.89 (0.83 to 0.96)), and the maximum number of drinks consumed on one occasion (0.96 (0.93 to 1.00), P=0.029), indicating significantly lower drinking outcomes in the intervention group than in the control group during the follow-up period. The intervention did not affect alcohol related consequences or academic performance. Conclusions Providing access to the smartphone application throughout the 12 month follow-up was effective at limiting the average drinking volume of university students who had self-reported unhealthy alcohol use at baseline. Trial registration ISRCTN 10007691.
18F-FDG PET/CT to Spare Malignancy in a Rare Case of Lung Endometriosis
Authors: Amanda Padilla Bermejo, Laura García Zoghby, Francisco José Pena Pardo, María del Prado Talavera Rubio, Víctor Manuel Poblete García
Journal: Clinical Nuclear Medicine (2023)

Lung endometriosis is a rare condition. A 44-year-old woman with known lung endometriosis and radiological follow-up showed progression of bilateral lung affection at control CT, with an enlarged solid nodule with respect to previous control. 18 F-FDG PET/CT was performed to assess that lesion and to guide biopsy. PET images showed the multiple known nodules with pathological tracer uptake.
Case 25-2023: An 18-Year-Old Man with Fever and Foot Pain
Authors: Daniel A. Rauch, Teresa Victoria, Heidi H. Pfeifer
Journal: New England Journal of Medicine (2023)

An 18-year-old man with the Dravet syndrome began to have fever and increased seizure activity. He had a 2-month history of foot swelling, and imaging revealed bone marrow edema and fractures. A diagnosis was made.
Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer
Authors: Timothy J. Whelan, Sally Smith, Sameer Parpia, Anthony W. Fyles, Anita Bane, Fei-Fei Liu, Eileen Rakovitch, Lynn Chang, Christiaan Stevens, Julie Bowen, Sawyna Provencher, Valerie Théberge, Anna Marie Mulligan, Zuzana Kos, Mohamed A. Akra, K. David Voduc, Tarek Hijal, Ian S. Dayes, Gregory Pond, James R. Wright, Torsten O. Nielsen, Mark N. Levine
Journal: New England Journal of Medicine (2023)

Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years.Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1).Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).
Headway against Brain Tumors with Molecular Targeting of IDH-Mutant Gliomas
Authors: David Schiff
Journal: New England Journal of Medicine (2023)

Approximately 2500 persons in the United States receive a diagnosis of isocitrate dehydrogenase (IDH)–mutated grade 2 glioma each year.1 These patients tend to be young (median age, 40 years), and most have tumor-related epilepsy and grapple with a tumor that may affect cognition, employment, and other aspects of life. These tumors typically become refractory to treatment and are eventually fatal, belying their designation as "low-grade" gliomas. Both fractionated radiotherapy and alkylator-based chemotherapy help control these tumors but convey a substantial risk of permanent toxic effects. With radiation therapy, such effects include fatigue, alopecia, radiation necrosis, and particularly, cognitive dysfunction; chemotherapy . . .
Reply to Wang <i>et al.</i>
Authors: Luca S. Menga, Luca Delle Cese, Domenico L. Grieco, Massimo Antonelli
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: The Proper Assessment of Pendelluft and Absolute End-Expiratory Lung Volume." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Gene Therapy in Patients with the Crigler–Najjar Syndrome
Authors: Lorenzo D’Antiga, Ulrich Beuers, Giuseppe Ronzitti, Nicola Brunetti-Pierri, Ulrich Baumann, Angelo Di Giorgio, Sem Aronson, Aurelie Hubert, Roberta Romano, Norman Junge, Piter Bosma, Giulia Bortolussi, Andrés F. Muro, Ravaka F. Soumoudronga, Philippe Veron, Fanny Collaud, Nathalie Knuchel-Legendre, Philippe Labrune, Federico Mingozzi
Journal: New England Journal of Medicine (2023)

Patients with the Crigler-Najjar syndrome lack the enzyme uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1), the absence of which leads to severe unconjugated hyperbilirubinemia that can cause irreversible neurologic injury and death. Prolonged, daily phototherapy partially controls the jaundice, but the only definitive cure is liver transplantation.We report the results of the dose-escalation portion of a phase 1-2 study evaluating the safety and efficacy of a single intravenous infusion of an adeno-associated virus serotype 8 vector encoding UGT1A1 in patients with the Crigler-Najjar syndrome that was being treated with phototherapy. Five patients received a single infusion of the gene construct (GNT0003): two received 2×1012 vector genomes (vg) per kilogram of body weight, and three received 5×1012 vg per kilogram. The primary end points were measures of safety and efficacy; efficacy was defined as a serum bilirubin level of 300 μmol per liter or lower measured at 17 weeks, 1 week after discontinuation of phototherapy.No serious adverse events were reported. The most common adverse events were headache and alterations in liver-enzyme levels. Alanine aminotransferase increased to levels above the upper limit of the normal range in four patients, a finding potentially related to an immune response against the infused vector; these patients were treated with a course of glucocorticoids. By week 16, serum bilirubin levels in patients who received the lower dose of GNT0003 exceeded 300 μmol per liter. The patients who received the higher dose had bilirubin levels below 300 μmol per liter in the absence of phototherapy at the end of follow-up (mean [±SD] baseline bilirubin level, 351±56 μmol per liter; mean level at the final follow-up visit [week 78 in two patients and week 80 in the other], 149±33 μmol per liter).No serious adverse events were reported in patients treated with the gene-therapy vector GNT0003 in this small study. Patients who received the higher dose had a decrease in bilirubin levels and were not receiving phototherapy at least 78 weeks after vector administration. (Funded by Genethon and others; ClinicalTrials.gov number, NCT03466463.).
A Case of Fetal-Induced Graft-versus-Host Disease
Authors: Anna R. Schreiber, Jennifer Santos, Brandon McMahon, Tyler W. Buckner, Courtney Olson, Michael O. Alberti, Amy Guimarães-Young, Christopher Knoeckel, Lindsey Broussard, Michael Aubrey, Brent E. Palmer, Emma Weiss, Geoffrey R. Connors, Selene Brunner, Joshua A. Wisell, Theresa Pacheco, Dara L. Aisner, Jonathan A. Gutman
Journal: New England Journal of Medicine (2023)
PB2385: CINOBUFAGIN PROMOTES APOPTOSIS OF DIFFUSE LARGE B LYMPHOMA CELLS BY INHIBITING UBIQUITINATION DEGRADATION OF TP53
Authors: Sanxiu He, Huihui Fu, LI Jun, Xiaomei Zhang, Yi Liu, Yao Liu
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Globally, there are 150,000 new cases of DLBCL each year, accounting for approximately 30% of all non-Hodgkin lymphoma cases. Although most patients can be cured with R-CHOP immunochemotherapy, 30-40% of patients progress or relapse after treatment. Therefore, there is an urgent need to find new treatments to improve the survival rate of this group of patients. Natural small molecule drugs have unique advantages as anticancer agents due to their low toxicity and multiple targets. Aims: In this study, we aims to explore potentially effective natural compounds as new therapeutic strategies for diffuse large B-cell lymphoma. Methods: Bioinformatics analysis was performed to find suitable natural compounds. The effects of natural compounds on the biological function of diffuse large B lymphoma cells were investigated by IC50 assay, cell apoptosis assay, cell cycle assay and mouse subcutaneous transplantation tumor model. 3D molecular simulation docking analysis, mRNA sequencing and WB assay were used to explore the molecular mechanism of natural compounds. Results: We identified 20 natural compounds targeting DLBCL prognostic related genes using GEO and CMAP databases. Among these drugs, Cinobufagin, a natural bufodienol isolated from toad venom, is the main research object of this subject due to its lower IC50 value. The results showed that Cinobufagin could effectively induce G2 phase arrest and apoptosis of diffuse large B lymphoma cells in vitro. Moreover, the drug significantly inhibited the growth of tumor tissue in the mouse model of heterotopic subcutaneous tumor transplantation. Through PharmMapper database and 3D molecular simulation docking analysis, we found that TP53’s E3 ubiquitin ligase MDM2 is a potential target of Cinobufagin. mRNA sequencing results also indicate that TP53 signaling pathway was activated after Cinobufagin treatment. Further WB experiment confirmed that Cinobufagin significantly up-regulated the expression level of TP53 protein in diffuse large B lymphoma cells. Summary/Conclusion: These results suggest that Cinobufagin can significantly inhibit the proliferation of diffuse large B-cell lymphoma at very low drug dose, and enhance the stability of TP53 by targeting MDM2 to play an anticancer role. Therefore, Cinobufagin has great potential application value as a new drug for the treatment of diffuse large B-cell lymphoma.Keywords: B cell lymphoma
PB2703: ISA-KD IN NOT TRANSPLANT CANDIDATES RRMM. EXPERIENCE IN REAL LIFE.
Authors: Dunia De Miguel Llorente, Nuria Golbano Lopez, Rocio Perez Alonso, Alejandro Vazquez Ramo, Ana Belen Santos Montero, Irene Nuevo Lopez, Marta Mora Argumanez, Helga Guillen Garcia, Angela Gil Perez
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Isatuximab+pomalidomide+dexamethasone (Isa-Pd) or Isa+carfilzomib+dexamethasone (Isa-Kd), respectively, are approved for patients with relapsed and/or refractory multiple myeloma (RRMM). Limited real-world evidence (RWE) exists for patients treated with Isa-Pd/Isa-Kd. Aims: Describe baseline characteristics, treatment exposure, and treatment-emergent adverse events (TEAEs) for Isa-treated RRMM patients in a real-world setting. Methods: We reported patients with relapsed MM with 1–3 prior lines of therapy. Patients were excluded if they had primary refractory MM, had received prior carfilzomib treatment, were refractory to anti-CD38 antibody therapy, or presented with left ventricular ejection fraction <40%. Patients with a baseline estimated glomerular filtration rate (eGFR) as low as 15 mL/min/1.73m² were and prior pulmonary comorbidities, including chronic obstructive pulmonary disease, were eligible. Patients received Isa intravenously at 10 mg/kg on days 1, 8, 15, and 22 in the first 28-day cycle; and days 1 and 15 in subsequent cycles. In both arms, carfilzomib was administered intravenously at 20 mg/m2 on days 1 and 2; 56 mg/m2 on days 8, 9, 15, and 16 of cycle 1; and then 56 mg/m2 on days 1, 2, 8, 9, 15, and 16 of subsequent cycles. Dexamethasone 20 mg was administered intravenously or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. The patients received acyclovir in prophylaxis treatment. Treatment continued until unacceptable adverse event (AE), disease progression, or other discontinuation criteria. Results: Between May-2022 and Feb-2023, 6 patients received ≥1 dose of Isa-Kd. Compared with baseline characteristics in Phase 3 Isa studies, a higher proportion of patients in our report 66% were ≥75 years old (median 75, range age 64-83) and ISS stage III, 50% of Isa-Kd patients had high-risk cytogenetics, and 66%, 17% and 17% of Isa-Kd patients received 1, 2 and ≥5 prior lines of therapy, respectively. 100%, 83%, 17% of patients were exposure to bortezomib, lenalidomida and pomalidomide. Everybody was naïve to antiCd38 therapy. At data cutoff, median (min–max) duration of Isa exposure was 3 (1-4) months, with 83.3% of patients still receiving Isa-Kd. For Isa-Kd, AEs occurred during treatment in 2 patients (2 (11.7%; pneumonia); and TEAEs leading to discontinuation in 0 patients. We don’t reported any infusion reactions. Response data are 40% CR, 60% VGBP. Summary/Conclusion: Isa-Kd has manageable safety profiles in routine clinical practice. These data provide RWE to support Isa use in RRMM outside clinical trials and in wider populations. We reported fast response, and well tolerated regimen in elderly patients. We don’t need to use G-CSF. Keywords: Multiple myeloma, Langerhans Cell Histiocytosis
PB2579: RISK FACTORS ASSOCIATED WITH MORTALITY OF BACILLUS CEREUS BACTEREMIA IN HEMATOLOGIC MALIGNANCIES.: CASE SERIES AND LITERATURE REVIEW
Authors: Tomohito Shimada, Kazuhiro Ishikawa, Nobuyoshi Mori
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background:Bacillus cereus (B. cereus) is a gram-positive rod widely distributed in nature and is generally known as a causative microorganism of food poisoning. Although rare, it can cause bloodstream infection through intravascular catheters and central nervous system (CNS) infection due to disseminated lesions, especially in immunosuppressed patients. However, few studies have had a large sample size of B. cereus bacteremia in patients with hematologic malignancies, and the risk factors, management, and prognosis. Aims: We investigate the risk factors, management, and prognosis of B. cereus bacteremia in patients with hematologic malignancies. Methods: Patients diagnosed with B. cereus bacteremia with hematologic malignancy were selected from cases at our hospital from April 2004 to May 2022. Also, we searched the electronic databases PubMed, Embase, and Ichushi on May 2022. Univariate analysis (χ2 test or Fisher’s exact probability ratio test) was performed with death as the outcome. Multivariate analysis (logistic regression analysis) was then performed on the factors that showed significant differences in univariate analysis. A p-value less than 0.05 was considered statistically different. Results: A total of 176 patients (8, 86, 3, and 79 cases were selected from our hospital, PubMed, Embase, and Ichushi, respectively), with a median age of 41 ± 26 years and 99 (56%) males. Acute leukemia accounted for 141 (80%) of the patients. Death occurred in 93 patients (53%). In univariate analysis, neutropenia, CNS infection, gastrointestinal infection, respiratory infection, glycopeptide antimicrobial use, and management with source control were significantly associated with death. Multivariate analysis showed that the odds ratios for death were significantly different in patients with CNS infection (OR; 3.49, 95% CI; 1.25-9.80), gastrointestinal infection (OR; 5.22, 95% CI; 1.82-15.0), respiratory infection (OR; 8.98, 95% CI; 1.62-49.9), glycopeptide antimicrobial use (OR; 0.10, 95% CI; 0.03-0.31), and management with source control (OR; 0.11, 95% CI; 0.03-0.37). Summary/Conclusion: Patients with acute leukemia are at high risk for B. cereus bacteremia and a high mortality rate. CNS, gastrointestinal and respiratory infections were independent risk factors for mortality, and management with source control and glycopeptide antimicrobial use were independent protective factors.Keywords: Febrile neutropenia, Acute leukemia, Infection
Participation rate and yield of two home-based screening methods to detect increased albuminuria in the general population in the Netherlands (THOMAS): a prospective, randomised, open-label implementation study
Authors: Dominique van Mil, Lyanne M Kieneker, Birgitte Evers-Roeten, Marc H M Thelen, Hanne de Vries, Marc H Hemmelder, Annemiek Dorgelo, Ronald W van Etten, Hiddo J L Heerspink, Ron T Gansevoort
Journal: The Lancet (2023)
The Proper Assessment of Pendelluft and Absolute End-Expiratory Lung Volume
Authors: Yuxian Wang, Jie Li, Ming Zhong, Zhanqi Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"The Proper Assessment of Pendelluft and Absolute End-Expiratory Lung Volume." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
PB2478: ASCIMINIB INDUCES ERYTHROPOIESIS IN CHRONIC MYELOID LEUKEMIA CELLS THROUGH DIFFERENTIATION AND NOT BY SELECTION
Authors: Hammad Hassan, Areeb Ahmed, Sarah Yousuf, Afsar Mian, El Nasir Lalani
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Tyrosine Kinase Inhibitors (TKIs) are shown to be effective in suppressing BCR-ABL1 expression and have been widely used in clinical settings. However, the application of TKIs in erythroid induction has remained a less explored area due to dose-limiting toxicities. In this study, we used asciminib, an allosteric inhibitor which specifically targets the ABL myristate pocket (STAMP), to evaluate its effectiveness in K562 cells for erythroid induction. Aims: To determine whether asciminib/ imatinib induces K562 cells to undergo differentiation or are the cells being specifically selected due to drug pressure. Methods: The K562 cells were sorted into three different populations based on their CD235a and CD71 expressions, where CD235a+/CD71+ is denoted as Q2, CD235a-/CD71- is denoted as Q3, and CD235a-/CD71+ is denoted as Q4. These sorted populations were subsequently cultured over a 6-day period in RPMI and EPO-based diﬀerentiation media in the absence and presence of TKIs (i.e.: 200nM imatinib and 10nM asciminib). CD235a and CD71 surface marker expressions were analyzed on the 6th day by flow cytometry to determine whether the erythroid induction is due to differentiation or by selection. Results: Asciminib was observed to drive erythroid induction through differentiation, as not only did the Q3 and Q4 populations survived the drug pressure but were also observed to be following their parental differentiation profile (i.e.: the transition from Q3 or Q4 to Q2) in both RPMI and EPO-based diﬀerentiation media. The EPO-based diﬀerentiation media gave survival advantage to the cells. The Q4 population contributed to ~50% of the parental populations` distribution and as indicated in the data, the Q4 population was less susceptible to asciminib; therefore, asciminib treated cells showed differentiation at earlier time points when compared to the imatinib treated cells. Summary/Conclusion: Our study demonstrates a novel application of asciminib in the erythroid differentiation of K562 cells. Asciminib promoted the erythroid-specific surface maker expression (CD235a/CD71). The data presented in this study may provide a basis for developing novel differentiation therapy for treating CML patients.Keywords: Erythroid lineage, Erythropoieisis, Erythroid differentiation